Administraion of rabbit or mouse anti-HSV-2 antibody (Neutralizing titer 1:128) to mice 8 to 48 hours after herpes simplex virus type 2 (HSV-2) inoculation protects animals from virus infection. The observed protection is not due solely to neutralization of virus in vivo since identical quantities of antibody do not protect sublethally irradiated animals. The objectives of this proposal are to identify the cellular and molecular basis of this resistance. A cellular basis for irradiation sensitivity of passive immunization will be examined by reconstruction experiments in which T-cells, B-cells and macrophages will be separated from heterogeneous populations of noncommitted cells (i.e., blood, spleen, peritoneal cavity) and individually tested for their ability to restore antibody mediated protection in irradiated recipients following administration of anti-HSV-2 sera. B-cells will be isolated from immune spleen cell preparations and examined for their potential to adoptively transfer anti-HSV-2 immunity in lieu of specific antibody. Complement activity following irradiation will also be correlated with antibody dependent immunity in vivo. If irradiation is found to reduce complement activity, the role of complement in antibody mediated resistance to HSV-2 will be determined by depleting complement in normal mice with cobra venom factor and testing for antibody mediated immunity in these animals. The role of IgG in the protection mechanisms will be examined. The Fc portion of IgG molecules isolated from anti-HSV-2 hyperimmune serum will be removed with pepsin and the resulting F(ab')2 fragments tested for their ability to passively transfer protection.